The Clinical Characteristics and Antimicrobial Resistance of Staphylococcus aureus Isolated from Patients with Staphylococcal Scalded Skin Syndrome (SSSS) in Southwestern China.

Staphylococcal scalded skin syndrome (SSSS) is a rare, toxin-mediated, desquamating bacterial infectious dermatosis. So far, data from Southwestern China is scarce. This study aimed to investigate the clinical characteristics of SSSS patients in our hospital, the relative proportion of methicillin-resistant Staphylococcus aureus (MRSA) in skin and soft tissue secretions, and the drug sensitivity of S. aureus to better assist dermatologists in the diagnosis and treatment of SSSS. We reviewed the demographic characteristics, clinical manifestations, treatment regimens, therapeutic efficacy, laboratory test results, drug sensitivity, and outcome data of 79 SSSS patients from January 2012 to December 2021. Statistical analysis was performed using t tests and chi-square tests. Among the 79 SSSS patients, MRSA was detected in 35 (44.3%) isolates: 34 community-acquired (CA)-MRSA (97.1%) and 1 hospital-acquired (HA)-MRSA. The SSSS incidence increased annually from 2012 to 2014 and then decreased gradually after peaking in 2015. All the isolates were sensitive to vancomycin, tigecycline, linezolid, moxifloxacin, levofloxacin, and ciprofloxacin; were completely resistant to penicillin; and had low sensitivity to clindamycin and erythromycin. Interestingly, the sensitivity of MRSA to tetracycline increased annually after 2015. The resistance rates to common drugs previously used to treat SSSS increased. These findings may accelerate diagnosis and improve empirical antibiotic use, suggesting that clinicians should prescribe drugs according to antimicrobial susceptibility.

Frequency and associated factors of accommodation and non-strabismic binocular vision dysfunction among medical university students.

AIM: To investigate the frequency and associated factors of accommodation and non-strabismic binocular vision dysfunction among medical university students. METHODS: Totally 158 student volunteers underwent routine vision examination in the optometry clinic of Guangxi Medical University. Their data were used to identify the different types of accommodation and non-strabismic binocular vision dysfunction and to determine their frequency. Correlation analysis and logistic regression were used to examine the factors associated with these abnormalities. RESULTS: The results showed that 36.71% of the subjects had accommodation and non-strabismic binocular vision issues, with 8.86% being attributed to accommodation dysfunction and 27.85% to binocular abnormalities. Convergence insufficiency (CI) was the most common abnormality, accounting for 13.29%. Those with these abnormalities experienced higher levels of eyestrain (χ2=69.518, P<0.001). The linear correlations were observed between the difference of binocular spherical equivalent (SE) and the index of horizontal esotropia at a distance (r=0.231, P=0.004) and the asthenopia survey scale (ASS) score (r=0.346, P<0.001). Furthermore, the right eye's SE was inversely correlated with the convergence of positive and negative fusion images at close range (r=-0.321, P<0.001), the convergence of negative fusion images at close range (r=-0.294, P<0.001), the vergence facility (VF; r=-0.234, P=0.003), and the set of negative fusion images at far range (r=-0.237, P=0.003). Logistic regression analysis indicated that gender, age, and the difference in right and binocular SE did not influence the emergence of these abnormalities. CONCLUSION: Binocular vision abnormalities are more prevalent than accommodation dysfunction, with CI being the most frequent type. Greater binocular refractive disparity leads to more severe eyestrain symptoms.

Chloroplast Protein Tic55 Involved in Dark-Induced Senescence through AtbHLH/AtWRKY-ANAC003 Controlling Pathway of Arabidopsis thaliana.

The chloroplast comprises the outer and inner membranes that are composed of the translocon protein complexes Toc and Tic (translocon at the outer/inner envelope membrane of chloroplasts), respectively. Tic55, a chloroplast Tic protein member, was shown to be not vital for functional protein import in Arabidopsis from previous studies. Instead, Tic55 was revealed to be a dark-induced senescence-related protein in our earlier study. To explore whether Tic55 elicits other biological functions, a tic55-II knockout mutant (SALK_086048) was characterized under different stress treatments. Abiotic stress conditions, such as cold, heat, and high osmotic pressure, did not cause visible effects on tic55-II mutant plant, when compared to the wild type (WT). In contrast, senescence was induced in the individually darkened leaves (IDLs), resulting in the differential expression of the senescence-related genes PEROXISOME DEFECTIVE 1 (PED1), BLUE COPPER-BINDING PROTEIN (BCB), SENESCENCE 1 (SEN1), and RUBISCO SMALL SUBUNIT GENE 2B (RBCS2B). The absence of Tic55 in tic55-II knockout mutant inhibited expression of the senescence-related genes PED1, BCB, and SEN1 at different stages of dark adaptation, while causing stimulation of RBCS2B gene expression at an early stage of dark response. Finally, yeast one-hybrid assays located the ANAC003 promoter region with cis-acting elements are responsible for binding to the different AtbHLH proteins, thereby causing the transactivation of an HIS3 reporter gene. ANAC003 was shown previously as a senescence-related protein and its activation would lead to expression of senescence-associated genes (SAGs), resulting in plant senescence. Thus, we propose a hypothetical model in which three signaling pathways may be involved in controlling the expression of ANAC003, followed by expression of SAGs that in turn leads to leaf senescence in Arabidopsis by this study and previous data.

Application of trastuzumab emtansine in HER-2-positive and KRAS/BRAF-mutated colon cancer cells.

BACKGROUND: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) for the treatment of human epidermal growth factor receptor 2 (HER-2)-positive breast cancer. T-DM1 is based on the trastuzumab antibody and delivers a toxic agent into breast cancer cells through endocytic mechanism. This study evaluated whether T-DM1 can be used in HER-2-positive colon cancer cells which harbour KRAS/ BRAF mutation with limited treatment. MATERIALS AND METHODS: LS174T and HT-29 which are KRAS and BRAF mutant HER-2-positive colon cancer cells were used in this study. Cells were first treated with T-DM1; cetuximab and trastuzumab were applied for comparison, the effect of drug sensitivity was determined. Cells were then transfected with plasmid to overexpress HER-2 or the endocytic protein, caveolin-1 or furthermore pretreated with metformin to examine the effect of T-DM1 efficacy. Finally, a xenograft mouse model was used to evaluate the drug efficacy in vivo. RESULTS: The results showed that T-DM1 had better inhibitory effect than cetuximab and trastuzumab on LS174T and HT-29 cells. HER-2 or caveolin-1 overexpression with plasmid in the cells to increase T-DM1 recognition or internalization can increase the sensitivity to T-DM1. When cells were pretreated with metformin, caveolin-1 expression was induced and promoted T-DM1 uptake and enhanced cell toxicity. In xenograft mouse model, combined treatment of T-DM1 and metformin had apparent inhibitory effect on subcutaneous tumour growth. CONCLUSION: The results of this study suggested that T-DM1 has potential in the treatment of HER-2-positive colon cancer cells, and application of metformin has therapeutic benefits during T-DM1 treatment.

The Direct Involvement of Dark-Induced Tic55 Protein in Chlorophyll Catabolism and Its Indirect Role in the MYB108-NAC Signaling Pathway during Leaf Senescence in Arabidopsis thaliana.

The chloroplast relies on proteins encoded in the nucleus, synthesized in the cytosol and subsequently transported into chloroplast through the protein complexes Toc and Tic (Translocon at the outer/inner membrane of chloroplasts). A Tic complex member, Tic55, contains a redox-related motif essential for protein import into chloroplasts in peas. However, Tic55 is not crucial for protein import in Arabidopsis. Here, a tic55-II-knockout mutant of Arabidopsis thaliana was characterized for Tic55 localization, its relationship with other translocon proteins, and its association with plant leaf senescence when compared to the wild type. Individually darkened leaves (IDLs) obtained through dark-induced leaf senescence were used to demonstrate chlorophyll breakdown and its relationship with plant senescence in the tic55-II-knockout mutant. The IDLs of the tic55-II-knockout mutant contained higher chlorophyll concentrations than those of the wild type. Our microarray analysis of IDLs during leaf senescence identified seven senescence-associated genes (SAGs) that were downregulated in the tic55-II-knockout mutant: ASP3, APG7, DIN2, DIN11, SAG12, SAG13, and YLS9. Real-time quantitative PCR confirmed the reliability of microarray analysis by showing the same expression patterns with those of the microarray data. Thus, Tic55 functions in dark-induced aging in A. thaliana by indirectly regulating downstream SAGs expression. In addition, the expression of four NAC genes, including ANAC003, ANAC010, ANAC042, and ANAC075 of IDL treated tic55-II-knockout mutant appeared to be downregulated. Yeast one hybrid assay revealed that only ANAC003 promoter region can be bound by MYB108, suggesting that a MYB-NAC regulatory network is involved in dark-stressed senescence.

Metformin-induced caveolin-1 expression promotes T-DM1 drug efficacy in breast cancer cells.

Trastuzumab emtansine (T-DM1) is an antibody drug conjugate (ADC) that was recently approved for the treatment of HER-2-positive metastatic breast cancer. The drug sensitivity of ADCs depends mainly on the internalization efficiency of the drug. Caveolin-1 was shown to promote T-DM1 internalization and enhance drug sensitivity. Whether caveolin-1 can be overexpressed to improve T-DM1 efficacy is interesting and has the potential for clinical application. In this study, diabetes drug metformin was investigated in terms of induction of caveolin-1 expression for increased efficacy of subsequent T-DM1 application. BT-474 cells were pretreated with metformin, followed by combined therapy with metformin and T-DM1. The T-DM1 internalization and drug efficacy were determined, and the protein expressions for signal transduction were also monitored. Caveolin-1 shRNA was applied to suppress endogenous caveolin-1 expression, and the ability of metformin to promote T-DM1 efficacy was investigated. Result showed that in BT-474 cells pretreated with metformin, cellular caveolin-1 overexpression was induced, which then promoted drug efficacy by enhancing T-DM1 internalization. As cellular caveolin-1 was suppressed by shRNA, the effect of metformin-enhanced T-DM1 cytotoxicity was decreased. This study demonstrated that metformin can be applied prior to T-DM1 treatment to improve the clinical efficacy of T-DM1 by enhancing caveolin-1-mediated endocytosis.

Rab11 collaborates E-cadherin to promote collective cell migration and indicates a poor prognosis in colorectal carcinoma.

BACKGROUND: Collective cell migration, whereby the cell-cell contacts such as E-cadherin are maintained during migration, has only recently emerged, and its detailed mechanisms are still unclear. In this study, the role of Rab11, which functions in recycling endosomes, and its relationship to E-cadherin in colorectal carcinoma were identified, and the role of Rab11 in the collective cell migration of colon cancer cells was clarified. MATERIALS AND METHODS: A total of 107 patients with surgically resected colorectal carcinoma were enrolled in this immunohistochemical study. Relationships between the overexpression of Rab11 and E-cadherin and survival were evaluated. The cell biology of Rab11 overexpression or knock-down in HT-29 colon cells was studied. RESULTS: The expression of Rab11 and E-cadherin was not correlated with the stage of cancer or lymph node metastasis. However, the overall survival was poor in the group of 67 patients with duo-positive Rab11 and E-cadherin expression compared to the group (40 patients) without dual-positive expression (P = 0·038). Rab11 was demonstrated to have a physical interaction with E-cadherin, and overexpression of Rab11 was found to promote collective cell migration through the increased distribution of E-cadherin, which enhanced cell-cell connections. In addition, Rac1 activation and matrix metalloproteinase-2 expressions were upregulated upon Rab11 expression. CONCLUSIONS: This study demonstrated that Rab11 and E-cadherin expressions are indicators of poor survival time in colorectal carcinoma, but that Rab11 overexpression may contribute to increased collective cell invasion in colorectal carcinoma.

Caveolin-1 Dependent Endocytosis Enhances the Chemosensitivity of HER-2 Positive Breast Cancer Cells to Trastuzumab Emtansine (T-DM1).

The humanized monoclonal antibody-drug conjugate trastuzumab emtansine (T-DM1, Kadcyla) has been approved by the U.S. FDA to treat human epidermal growth factor receptor 2 (HER-2)-positive metastatic breast cancer. Despite its effectiveness in most patients, some are initially resistant or develop resistance. No biomarker of drug resistance to T-DM1 has been identified. Antibody-drug efficacy is associated with antibody internalization in the cell; therefore, cellular sensitivity of cells to the drug may be linked to cellular vesicle trafficking systems. Caveolin-1 is a 22 KD protein required for caveolae formation and endocytic membrane transport. In this study, the relationship between caveolin-1 expression and the chemosensitivity of HER-2-positive breast cancer cells to T-DM1 was investigated. Samples from 32 human breast cancer biopsy and normal tissue specimens were evaluated immunohistochemically for caveolin-1 expression. Caveolin-1 was shown to be expressed in 68% (22/32) of the breast cancer specimens. In addition, eight (72.7%, 8/11) HER-2 positive breast cancer specimens had a higher caveolin-1 expression than normal tissues. HER-2-positive BT-474 and SKBR-3 breast cancer cells that express low and moderate levels of caveolin-1, respectively, were treated with trastuzumab or its conjugate T-DM1. Cell viability and molecular localizations of caveolin-1, antibody and its conjugate were examined. Confocal microscopy showed that T-DM1 and caveolin-1 colocalized in SKBR-3 cells, which also were five times more sensitive to the conjugate in terms of cell survival than BT-474 cells, although T-DM1 also showed improved drug efficacy in BT-474 cells than trastuzumab treatment. Caveolin-1 expression in these lines was manipulated by transfection of GFP-tagged caveolin-1 or caveolin-1 siRNA. BT-474 cells overexpressing caveolin-1 were more sensitive to T-DM1 treatment than mock-transfected cells, whereas the siRNA-transfected SKBR-3 cells had decreased sensitivity to T-DM1 than mock-transfected SKBR-3 cells. The expression of caveolin-1 could mediate endocytosis and promote the internalization of T-DM1 into HER-2 positive cancer cells. Thus, caveolin-1 protein may be an effective predictor for determining the outcome of T-DM1 treatment in breast cancer patients.

Rab11 regulates E-cadherin expression and induces cell transformation in colorectal carcinoma.

BACKGROUND: In the process of epithelial mesenchymal transition EMT, the disassembly of junctional adhesion complexes such as E-cadherin is a remarkable sign during changes in cell morphology and polarity. However, E-cadherin expression is dynamic, and is regulated by the cellular endocytic system; it is also involved in cell signaling mechanisms. In this study, we investigated the role of E-cadherin in colorectal tumors and the relationship with recycling endosome protein Rab11 in colon cell transformation. METHODS: For tissue screening, the expressions of E-cadherin and Rab11 in colorectal tumors were identified by immunohistochemistry in 113 patients with colorectal carcinoma. For the in vitro cell experiment, GFP-tagged Rab11 plasmid was transfected into HT29 colon cells, E-cadherin expression and cell transformation were monitored by Western blot and confocal microscopy. RESULTS: In immunohistochemistry, the mean score of E-cadherin in tumor and normal tissues was 1.41 ± 0.06 and 1.08 ± 0.06 (p < 0.05). The mean score of Rab11 in tumor and normal tissues was 0.51 ± 0.05 and 0.18 ± 0.02 (p < 0.05). Synchronous overexpression of E-cadherin and Rab11 was noted in 74 patients (66.5%) with colorectal carcinoma. When GFP-tagged Rab11 plasmid was overexpressed in cultured colon cell line HT-29, the E-cadherin expression was up-regulated, and cell membrane protrusion was induced, which resulted in cell transformation and cell migration. CONCLUSIONS: This study demonstrated the importance of the overexpression of Rab11 and E-cadherin in colorectal cancer. The results indicated that Rab11 together with E-cadherin might be potential markers for colorectal cancer progression and treatment.